Since AIDS was discovered 30 years ago, the Human Immunodeficiency Virus that causes it, HIV, has infected more than 60 million people and killed nearly half of them. Two-thirds of sufferers are in Africa and one in ten is a child, and a final push is underway to get the new generation of anti-HIV drugs to every person known to have the virus.

US Secretary of State Hillary Clinton promised at a recent international AIDS conference in Washington that this new campaign would result in an AIDS-free generation. But is this true?

Rear Vision looks back on the origins of HIV-AIDS and the struggle to contain it, as well as the attempts to use new tools in gene therapy and stem cell research to permanently cure those already infected with the virus.

Transcript

Hillary Clinton (archival): So many people all over the world have not been satisfied that we have done enough. And I am here to set a goal for a generation that is free of AIDS.

Ian Townsend: Since AIDS was discovered 30 years ago, the Human Immunodeficiency Virus that causes it, HIV, has infected more than 60 million people and killed nearly half of them.

Recently, at an international AIDS conference in Washington, US Secretary of State, Hillary Clinton, promised that an AIDS-free generation was around the corner.

Hillary Clinton (archival): This is a fight we can win. We have already come so far, too far to stop now. Let me begin by defining what we mean by an AIDS-free generation: it is a time when, first of all, virtually no child anywhere will be born with the virus. (Applause)

Ian Townsend: Hello, I’m Ian Townsend and welcome to Rear Vision on RN, Radio Australia and the web.

Around the world, 34 million people are now living with HIV/AIDS. Two-thirds of them are in Africa and one in ten is a child, and so a final push is underway to get the new generation of anti-HIV drugs to every person known to have the virus.

Thanks to those new drugs, HIV/AIDS is no longer the death sentence it used to be in developed countries such as Australia. The remarkable advances over the years in drug research have helped a former teacher from Melbourne, David Menadue, live with HIV for three decades.

David Menadue: My estimate may be that it was 1982 I picked it up, because I had a strange flu-like thing happen to me when I was in Sydney for Mardi Gras. And so I think probably that means, you know, seven years; ’89 I developed a pneumonia that’s peculiar to HIV called Pneumocystis carinii pneumonia, and I was told I probably had about a year to live. But fortunately that wasn’t the case.

Ian Townsend: The HIV virus, too, has been a great survivor. It originated in chimpanzees in central Africa, from a virus called Simian Immunodeficiency Virus, and new research has now discovered when the chimpanzee virus, SIV, jumped to humans, evolved into the human virus, HIV-1, and started one of the world’s deadliest pandemics.

Professor of infectious disease at the University of Sherbrooke in Canada, Dr Jacques Pepin, has traced it all back to one hunter in central Africa nearly a century ago.

Jacques Pepin: And we believe that the first case, the one who started the pandemic, was probably a hunter, or if not the hunter maybe the hunter’s wife. This person probably injured himself or injured herself while cutting out the chimpanzee meat and then the virus was transmitted from the chimpanzee to the first human being.

This event, the first cross-species transmission event, occurred at some point in the first three decades of the twentieth century, so somewhere between 1908 and 1921.

Ian Townsend: Those dates come from mathematical modelling, based on the time it takes for genes in the virus to change and then working back from today’s HIV and SIV viruses to see when they had a common ancestor. It’s a calculation based on what’s called a molecular clock. Dr Pepin’s molecular clock says the most likely date for the crossover was the decade or so before 1921.

After that first person was infected, a series of unfortunate events helped the virus spread. In the 1920s and ‘30s, the colonial powers in Central Africa, particularly the French and the Belgians, began big public health campaigns, going from village to village, identifying sick people and injecting them with drugs.

Jacques Pepin: And these injections were done with syringes and needles that were constantly reused without proper sterilisation. So I believe that that first, very first, case—the hunter or maybe the hunter’s wife—was treated in the village for some tropical disease and through the injections there was transmission to other patients who were receiving similar treatments at the same place at the same time.

And then at some point an infected person managed to reach one of the emergent cities of the region, of central Africa. In these cities, and especially so in Leopoldville, which was the capital of the Belgian Congo, for a number of reasons there was a very substantial excess in the number of adult males compared to the number of adult women and that drove the development of prostitution within these cities.

When an infected person reached the city and managed to transmit the virus sexually to a prostitute that would set the stage for the second component of the amplification, and this time it was the sexual transmission.

Newsreel voiceover (archival): Violence and chaos in the Congo. Barely eleven days after official independence from Belgium, Congolese troops mutinied and began a wave of attacks and looting throughout the far-flung sectors of the former colony.

Jacques Pepin: From the Congo it eventually managed to spread to Haiti. It was a consequence of the chaos that followed the independence of the Congo in 1960. So basically the health system, the school system and so on collapsed and they had to be replaced with Haitians. And about four-and-a-half thousand of them went to work in the Congo for several years.

Newsreel voiceover (archival): …reign of terror, a harsh awakening to reality from golden dreams of independence.

Jacques Pepin: We think it probably arrived in Haiti at the end of the 1960s, maybe ‘67 or ‘68, and about three years later it travelled from Haiti to the US. It probably arrived in the US around 1971. And then on average, after you get infected the incubation period for the development of AIDS is about ten years on average. So cases of AIDS started developing in the late 1970s, but by 1981 they were accumulating to such a point that some doctors in California recognised that there was a new disease going on over there.

Journalist (archival): A newly discovered form of cancer which affects male homosexuals is causing concern in the United States. According to TheNew England Journal of Medicine, the disease appears to affect those who take drugs and is sexually transmitted. Terry Hughes in New York is speaking to the chief of the Division of Infectious Diseases at Duke University in North Carolina, Dr Durack.

David Durack (archival): The Centers for Disease Control received a surprising number of case reports of young homosexual males who’d previously been perfectly healthy…

Ian Townsend: Dr David Harrich, now an HIV researcher at the Queensland Institute of Medical Research, was in Los Angeles when doctors first noticed clusters of rare cancers.

David Harrich: Dr Michael Gottlieb in 1981 had identified five men and termed the disease as AIDS, Acquired Immunodeficiency Syndrome, because nobody knew what was causing this. And one thing they noticed was that these people got pneumocystis pneumonia, which is really unheard of in the general population. And all these men were getting very sick and nobody knew what was the cause.

David Durack (archival): Some of them developed a very unusual skin tumour called Kaposi’s sarcoma, while others developed pneumocystis pneumonia, which is a rather rare type of pneumonia that usually occurs in compromised patients; that is, patients whose first defences have been debilitated in some way. Now, what we don’t know is whether all homosexuals are at risk for it, and our guess is probably not. We feel that probably it is a subgroup who are predisposed in some way, possibly by their genetic makeup, possibly by drugs, possibly by a virus.

Ian Townsend: Back in Australia, the virus was already infecting people, but no one knew it at the time. David Menadue was living in Melbourne in the early 1980s.

David Menadue: The first Australian case occurred in 1983, an American tourist in Melbourne. And we in the gay community particularly—because we knew we were the most at risk for whatever reason, we didn’t know why—but people in the gay community felt, ‘Oh well, we haven’t been to America,’ or you know, ‘We haven’t had sex with an American. We must be okay,’ which was rubbish of course, because it was circulating in our society in the early ‘80s. And we know people who picked it up in the early ‘80s. Their blood tests have shown that they’ve had it since the early ‘80s, maybe even the late ‘70s.

Journalist (archival): The French team, working at the Pasteur institute in Paris, announced last week what it believes is probably the cause of AIDS, a virus they call ‘LAV’, short for lymphadenopathy virus. Now the Americans have come up with their own candidate, a virus they call ‘human T-cell lymphotropic virus 3’ or HTLV-3.

One of the questions now is whether LAV and HTLV-3 are actually the same thing. Independent scientists say there’s a fair chance they are. Assistant Secretary for Health in the Reagan administration, Edward Brandt:

Edward Brandt (archival): That will allow us to do two things. One, it will allow us to screen for transfusions. Second is that we should be able to develop a vaccine over the next few years; it’s not something that’s going to happen right away.

Ian Townsend: That was 1984. While that vaccine is still eluding researchers, a test for the HIV virus came out fast. In Melbourne, David Menadue wasn’t feeling well and decided to get the test.

David Menadue: So I went in in October and I got the positive result and I thought, ‘Oh well, if I am everybody else must be.’ And that was the rude shock I got, because not only were quite a lot of my friends who tested negative, a whole lot of my friends wouldn’t get tested because they thought ‘What’s the point? There are no treatments, I’m just going to experience this huge amount of stress knowing I’m HIV positive and I might lose my job or I might be discriminated against. So I won’t test.’ Because I was one of the first people, I felt very lonely.

Ian Townsend: Over in the United States, though, the number of AIDS patients was growing more rapidly and sparking a lot of frantic research. David Harrich was in Los Angeles working as a research assistant at UCLA, looking at this newly discovered virus under a microscope.

David Harrich: And at that time there were no therapies for HIV, there were no drugs, and we really didn’t know very much about the virus or how it was transmitted or what it could do. And so I started in a lab that at the time was pretty risky. By 1985, Dr Robert Gallo and Jean Luc Montagnier in the Pasteur Institute and Françoise Barré-Sinoussi had identified the virus. And so we knew what it was, but we really needed all the tools to get at how it grew in people; you know, what it required.

Ian Townsend: What was it like back then? There must have been a great element of uncertainty about what on earth this was.

David Harrich: Well, it was an open book. We didn’t… as a molecular biologist we want to know… These viruses are parasites, essentially. They have to get into a cell and use the cellular machinery so that they can replicate themselves. And we needed to find out what the cellular factors were and how they helped the virus and what were the essential… We didn’t even know what the essential viral genes were at the time. So we were nutting those out one at a time and figuring out how they all worked. So that took quite a few years.

David Menadue: My doctor said I was diagnosed and I didn’t know whether to be shocked or what. I mean, everybody knew that AIDS killed people and I said, ‘What do you think my chances are?’ And he said, ‘Well, we think at this stage it’ll be a bit like hepatitis B, you know, where you can develop antibodies and never actually go on to get the illness itself.’ And I thought, oh well, ten per cent chance is what he was saying of me actually getting AIDS. I thought 90 per cent; I was in my early thirties and I was feeling a bit impervious to disease or anything that was going to bring me down. And I felt, oh, that’ll be all right.

But of course as the ‘80s unfolded we discovered that possibly more like 100 per cent of people were going to get AIDS, because the virus didn’t… antibodies didn’t work to the virus in your body.

David Harrich: I think there was a sense of urgency. There wasn’t a fear among the research workers, because we knew how to protect ourselves, so that was not a problem. And there had been very few incidences of research workers becoming infected—there’s been a couple of cases, but it’s very rare. So we knew what we were doing at the time, yeah.

Ian Townsend: So what were the treatments available back in ‘85?

David Harrich: None. Zero. It wasn’t until 1986, and I think it became FDA-approved in 1987, that we had the first drug, which was AZT.

David Menadue: The later ‘80s, early ‘90s was what I’d call a period of desperation, because doctors just could not save people and people were dying every month and I was going to a funeral every month. And… ‘People were dying every month’—what am I saying?—every week, sometimes every day, in hospitals.

And the community didn’t quite know how to get the level of response they needed. Like, we needed a drug called AZT funded, we thought. We thought it was going to be a great saviour drug—it turned out to be quite flawed. But…

So you had a group called ACT UP, AIDS Coalition To Unleash Power, which was doing a lot of stirring, shall we say, in the community. I mean, in Melbourne they ripped up the floral clock and put little crosses there. And that sort of thing, that sort of activist protest, which of course brought the ire of a lot of the press for the irresponsibility but actually kind of worked, because the drug laws in this country were very restrictive and people were dying. We didn’t accept that.

So people got to the streets and said, ‘No, you’ll have to overhaul this, you have to change it and try and save lives.’ And fortunately the government did.

Ian Townsend: And you mentioned that AZT was flawed?

David Menadue: Absolutely. There was a huge backlash against it, because people started to think that AZT was actually causing people’s deaths rather than helping people. Because it was being used at a really high dose—it’s still used in some places; not in Australia very much but in developing countries, but at a much lower dose. What we didn’t realise is it was stripping the fat and muscle off people. It was contributing to that. I mean, HIV does that anyway, but it was accelerating the process.

Ian Townsend: This is Rear Vision on ABC RN and Radio Australia. I’m Ian Townsend and we’re looking at the origins of HIV/AIDS and the struggle to deal with the pandemic.

Back in the mid 1980s, as researchers were pulling the virus apart to see how it worked, out in the community there was ignorance and fear.

David Menadue: You know, I remember a headline in the Melbourne Truth, ‘Die you deviant’, because a gay man had gone into a blood bank—I think it was actually in Queensland—and donated blood, not knowing he was HIV positive. And then it was later discovered that that infected a number of babies. And, you know, the suggestion that the person himself was the villain became part of that kind of ‘us and them’ thinking that a lot of positive people had, that everyone thought we were the vectors of transmission, so therefore we had to be stopped in our tracks.

And I was really distressed and highly stigmatised to hear, see front page stories from some of the more unenlightened commentators saying that we needed to be quarantined, and hospital workers refusing to give food to patients, to actually walk in their rooms. And that sort of overreaction in society, it needed leadership to hose that down and I’m very glad that we got that. I’m very glad that the government at the time saw fit to take a practical view of this, try and educate the community about what the actual risks were. I mean, it was the Grim Reaper campaign, of course, I’m particularly talking about that took the public’s imagination or fear or whatever, but it took their attention.

Grim Reaper advertisement (archival):‘At first only gays and IV drug users were being killed by AIDS, but now we know every one of us could be devastated by it. The fact is, over 50,000 men, women and children now carry the AIDS virus, that in three years nearly 2000 of us will be dead. But if not stopped, it could kill more Australians than World War II. But AIDS can be stopped and you can help stop it. If you have sex, have just one safe partner or always use condoms. Always.’

David Menadue: We would sit in front of the Grim Reaper campaign and laugh at it, because that was our way of treating it with black humour, because we felt the Grim Reaper was us. It wasn’t a virus; it was representing positive people with our little skeletal cheeks and our skinny arms and legs. And so we would make a joke about it.

And that was a good thing for our mental health, but then people in my group—and we had about 30 in it at one stage—started to die. And so every funeral you went to you thought, ‘Well, am I going to be next?’ And it’s an awful factor, I suppose, but you would look around and say, ‘Well, who’s looking well today?’ It was that sort of stuff, and I knew people were thinking the same thing for me. And many years later people told me they thought many times I was going to go. And that’s… that was just the way it was. There was no real way of stopping what was going on until the mid-’90s when we had a whole new lot of treatments.

David Harrich: Over the years, I would say in the last ten years, there’s just been an explosion of HIV drugs and combination drugs. So there’s still a lot of research into various combinations, trying to get the anti-viral drugs down to a manageable number and a manageable number of pills a day. So it used to be you had to have an entire cabinet and organise your pills as to what you… whether you took it… you might have 20 pills a day and some in the morning and some in the afternoon, some with food some not on food. You almost needed a bachelor’s degree of science to understand how you took all these pills.

David Menadue: Literally every four hours. I would have to get up at 4am in the morning and then again at 8am and so forth all through the day. And I was overdosing myself on this drug, because they didn’t understand the drug troughs meant there were times during the night, for instance, that it didn’t matter, that your drug levels were high or that they’ve carried on through your blood system in different ways than they understood.

So a lot of us ended up with blood transfusions and really low blood counts from taking these toxic drugs. And really all through the ‘90s there were some incredible side effects, like problems with your pancreas and extreme diarrhoea. And a lot of people didn’t want to take the pills because they saw how awful the side effects were.

Ian Townsend: Why does it take so many drugs to keep it under control?

David Harrich: Well, HIV can become resistant to a single drug in days if not a week because it grows so rapidly. And it’s a virus that is known to be error-prone, so what that means is as it’s copying the RNA, occasionally it makes a mistake. HIV will make one, two or three mistakes each and every time.

But when it’s making ten to the tenth virus particles… so that’s an astronomical number—in each day if you’re untreated, HIV is making ten to the tenth copies of itself—ten to the tenth. If it makes a change once in every position, eventually it will come up with a way or a mutation in a protein that makes it resistant to the drug.

Ian Townsend: So it was evolving?

David Harrich: Oh, HIV, that’s what HIV is very good at. It’s a very adaptive virus. It’s very adaptive with respect to drug therapy, it’s very adaptive with respect to immune responses, and so it’s a very tricky customer. So as it comes across obstacles to replication it comes up with solutions and it’s very good at it.

David Menadue: In 1996 we had a group of drugs called protease inhibitors and even today they are called the nuclear bombs of anti-HIV treatment. Most people don’t go on them first, because they have certain side effects, which we discovered later. You know, in the ‘90s as we started to develop little pot tummies and high cholesterol and high triglycerides and a lot of diarrhoea and so forth, these drugs were flawed as well, but they were much more effective at keeping people alive.

So, I’m still on some of those protease inhibitors, but they’ve improved so much. And now we have a whole new lot of generations of drugs that are completely different and virtually side effect free. The longer you’re on them of course you need to monitor things like your kidneys and your liver and so forth, but as a general rule it’s a chronic manageable disease now and the HIV drugs have made it so.

Ian Townsend: But an actual vaccine or cure has remained elusive. For many years people stopped talking about a cure because the virus managed to beat every attempt to eradicate it.

So it came as a surprise when one man was cured in 2007, after having a bone marrow transplant. His case has recently come to light, and he’s now known as ‘the Berlin Patient’.

Journalist (archival): His name is Timothy Ray Brown, a 45-year-old man now living in the Bay Area who tested positive for HIV back in 1995 but who now has entered the scientific journals as the first man in world history to have his HIV completely eliminated from his body. It’s what doctors call a ‘functional cure’.

He was living in Berlin, Germany, in 2007, dealing with HIV and leukaemia, when scientists there gave him a bone marrow stem cell transplant that had astounding results.

Timothy Ray Brown (archival): I quit taking my HIV medication on the day that I got the transplant and haven’t had to take any since.

Journalist (archival): It’s amazing.

Timothy Ray Brown (archival): Yeah. The leukaemia came back…

David Harrich: The Berlin Patient; this is the first and only person cured from the disease. He had HIV and he came down with leukaemia. And his German doctor fortunately didn’t know a lot about HIV at the time and just thought, ‘Well, you know what, he needs a bone marrow transplant; let’s give him bone marrow from a person that’s a match, that has this gene mutation…’ So this gene mutation makes your cells resistant to HIV.

And they gave him a bone marrow transplant from such a person, treated him, and five years later now, without drugs for five years, he has no HIV at all. He’s the first person to be cured of HIV. But this is along the lines of gene therapy, except that it’s natural gene therapy because it’s a natural mutation. Probably one… you could think one downside of this therapy is that he’s now on immunosuppressive drugs, because he has a bone marrow transplant. So it’s not a perfect solution at all, but it’s encouraging that there is a possibility to cure HIV.

Ian Townsend: David Harrich at QIMR is part of a worldwide effort looking for a cure for AIDS, using new tools in gene therapy and stem cells. The idea is to modify human cells with a gene mutation that makes those cells resistant to HIV infection.

David Harrich: And then when you have enough of these cells and you reintroduce them back into the patient—so it’s the patient’s own cells—they then develop into an entire immune system or immune cells that are now resistant to the virus that they harbour. So it gives them a chance actually to be cured of HIV, or if HIV remains it still allows you… HIV doesn’t necessarily kill you. What happens is it’s immune depletion and you become susceptible to a lot of other infectious diseases and cancers. So that would allow you then to deal with those potential threats and presumably HIV would slowly disappear anyway because it couldn’t grow. So that’s sort of a… that’s a future aim of ours and we’re working on that today in the lab.

Ian Townsend: Meanwhile, David Menadue has, remarkably, survived for almost as long as the virus has had that name, HIV.

David Menadue: Twenty-eight years. Look, I don’t have any particular reason to ascribe to that, but I do think good medical advice over the years, good fortune, really, to be able to stay alive long enough to take those treatments in the mid-‘90s. They were the things that really saved me. I was up to about six AIDS-defining illnesses then and, look, everyone said, ‘Your next one is going to be too much.’ And, look, so many of my friends went in that period and they still live with me and that period and that grief still lives with me. But some of us were lucky and unfortunately some of us weren’t… and anyway…

Ian Townsend: AIDS survivor David Menadue ending today’s Rear Vision. Our other guests were Dr David Harrich of the Queensland Institute of Medical Research, and Professor Jacques Pepin from Sherbrooke University in Canada.